System error compensation of analyte concentration determinations based on pseudo-reference concentration and signal-based anchor parameters

Abstract

During analyte analysis, errors may be introduced into an analysis by both the biosensor system used to perform the analysis and by errors in the output signal measured by the measurement device of the biosensor. For a reference sample, system error may be determined through the determination of relative error. However, during an analysis of a test sample with the measurement device of the biosensor system, true relative error cannot be known. A pseudo-reference concentration determined during the analysis may be used as a substitute for true relative error. The present invention introduces the determination of a pseudo-reference concentration determined during the analysis as a substitute for the true relative error and uses an anchor parameter to compensate for the system error in the analysis-determined pseudo-reference concentration.

What is claimed is: 
     
       1. A method of operating a biosensor system for determining signal-based anchor parameters, the method comprising:
 providing a biosensor system comprising:
 a measurement device having electrical circuitry communicatively coupled to a processor, a storage medium, a signal generator, and a sensor interface, the processor having instructions and data stored in the storage medium, and a test sensor having a base and a sample interface, the base forming a reservoir and a channel with an opening, the reservoir being in electrical or optical communication with the measurement device; 
 
 measuring, one or more analyte responsive output signals from a reference sample, wherein the one or more analyte responsive output signals are indicative of an effect of one or more extraneous stimuli on the reference sample, 
 determining a normalizing relationship based on linear or non-linear regression of the one or more analyte responsive output signals; 
 storing the normalizing relationship in the storage medium, wherein the normalizing relationship is stored as part of calibration information used for calibrating the biosensor system to account for the one or more extraneous stimuli; 
 responsive to receiving a biological fluid sample, applying an electrical or optical input signal to generate an input signal from the signal generator; 
 generating at least one analyte responsive output signal, wherein the one or more analyte responsive output signals is an electrical output signal generated by a redox reaction or a light-generated output signal in response to a light-identifiable species; 
 determining an initial analyte concentration of the biological fluid sample based on the at least one analyte responsive output signal; 
 determining, using the normalizing relationship, at least one normalized output signal from the at least one analyte responsive output signal; 
 determining, a pseudo-reference concentration value of the biological fluid sample, 
 wherein the pseudo-reference concentration value is a substitute for true relative error; 
 determining at least one corresponding normalized output signal by selecting at least one reference sample analyte concentration from a plurality of stored reference sample analyte concentration and a normalized reference correlation; 
 determining a system error for the at least one analyte responsive output signal through a comparison of the initial analyte concentration and the at least one reference sample analyte concentration, 
 wherein the system error contributes to inaccurate analyte concentration determinations; 
 responsive to determining the system error, determining at least one signal-based anchor parameter based on a comparison of the pseudo-reference concentration value and the at least one corresponding normalized output signal, wherein the at least one signal-based anchor parameter compensates for the system error; 
 incorporating the at least one signal-based anchor parameter into a compensation relationship, wherein the compensation relationship compensates for inaccuracies caused by the system error; 
 determining a final compensated analyte concentration of the biological fluid sample based at least in part on the compensation relationship and the initial analyte concentration of the biological fluid sample; and 
 outputting the final compensated analyte concentration to one or more of a display, a remote receiver, or a storage medium. 
 
     
     
       2. The method of  claim 1 , wherein the determining of the at least one normalized output signal comprises transforming the at least one analyte responsive output signal with a normalizing relationship. 
     
     
       3. The method of  claim 1 , wherein the determining of the pseudo-reference concentration value comprises selecting a sample analyte concentration value as the pseudo-reference concentration value, where the sample analyte concentration value for multiple analyses being on average closer to an actual analyte concentration of the biological fluid sample than would be independently determined from at least two analyte responsive output signals. 
     
     
       4. The method of  claim 3 , wherein the determining of the pseudo-reference concentration value comprises determining at least two initial analyte concentrations of the biological fluid sample from the at least two analyte responsive output signals; and from the biological fluid sample averaging the at least two initial analyte concentrations. 
     
     
       5. The method of  claim 3 , wherein the determining of the pseudo-reference concentration value comprises initially averaging the at least two analyte responsive output signals; and determining the pseudo-reference concentration value from an averaged output signal. 
     
     
       6. The method of  claim 1 , wherein the determining of the system error comprises determining system error for a group of output signal values. 
     
     
       7. The method of  claim 1 , wherein the determining of the system error comprises determining system error for at least two initial analyte concentrations and at least two reference sample analyte concentrations. 
     
     
       8. The method of  claim 7 , wherein the determining of the system error comprises subtracting one of the two reference sample analyte concentrations from one of the two initial analyte concentrations and dividing by the one of the two reference sample analyte concentration. 
     
     
       9. The method of  claim 1 , wherein the determining of the at least one signal-based anchor parameter comprises subtracting at least one pseudo-reference signal from the at least one normalized output signal and dividing by the at least one pseudo-reference signal. 
     
     
       10. The method of  claim 2 , further comprising:
 determining the normalizing relationship between at least two analyte responsive output signals and at least two quantified extraneous stimulus values, where the at least two analyte responsive output signals being affected by at least one extraneous stimulus; 
 determining the at least two quantified extraneous stimulus values from at least one extraneous stimulus responsive output signal; 
 measuring at least one extraneous stimulus responsive output signal from at least one reference sample; and 
 determining a reference correlation between a reference sample analyte concentration of the at least one reference sample and the at least two analyte responsive output signals. 
 
     
     
       11. The method of  claim 10 , wherein the determining of the normalizing relationship comprises applying a regression technique to the at least two analyte responsive output signals and the at least two quantified extraneous stimulus values at a single selected analyte concentration. 
     
     
       12. The method of  claim 10 , further comprising:
 determining the normalized reference correlation between at least two normalized analyte responsive output signals and the at least one reference sample analyte concentration; and 
 determining the at least two normalized analyte responsive output signals from the at least two analyte responsive output signals and a normalizing value generated from the normalizing relationship. 
 
     
     
       13. The method of  claim 12 , wherein the determining of the normalized reference correlation comprises applying a regression technique to the at least two normalized analyte responsive output signals and the at least one reference sample analyte concentration. 
     
     
       14. The method of  claim 12 , further comprising:
 determining at least two second quantified extraneous stimulus values from the at least one extraneous stimulus responsive output signal; 
 determining a second normalizing relationship between the at least two normalized analyte responsive output signals and the at least two second quantified extraneous stimulus values; and 
 determining the at least two normalized analyte responsive output signal in response to the at least one reference sample analyte concentration and the second normalizing relationship. 
 
     
     
       15. The method of  claim 14 , wherein the determining of the second normalizing relationship comprises applying a regression technique to the at least two normalized analyte responsive output signals and the at least two second quantified extraneous stimulus values at a single selected analyte concentration. 
     
     
       16. The method of  claim 14 , further comprising:
 determining at least two second normalized analyte responsive output signals from the at least two normalized analyte responsive output signals and a second normalizing value; 
 determining a second normalized reference correlation between the at least two second normalized analyte responsive output signals and the at least one reference sample analyte concentration; and 
 determining the at least one corresponding normalized output signal in response to the at least one reference sample analyte concentration and the second normalized reference correlation. 
 
     
     
       17. The method of  claim 16 , wherein the determining of the second normalized reference correlation comprises applying a regression technique to the at least two second normalized analyte responsive output signals and the at least one reference sample analyte concentration. 
     
     
       18. The method of  claim 10 , wherein the at least one extraneous stimulus is at least one of a physical characteristic, an environmental aspect, and a manufacturing variation. 
     
     
       19. The method of  claim 10 , wherein the at least one extraneous stimulus is at least one of temperature, total hemoglobin, and hematocrit. 
     
     
       20. A biosensor system for determining an analyte concentration in a biological fluid sample, the biosensor system being an optical system or an electrochemical system, the biosensor system comprising:
 a test sensor having a base and a sample interface, the base forming a reservoir and a channel with an opening, the opening being configured to receive a biological fluid sample and to allow the biological fluid sample to flow through the channel to fill at least in part the reservoir; and 
 a measurement device in electrical or optical communication with the reservoir, the measurement device having electrical circuitry communicatively coupled to a processor, a storage medium, a signal generator, and a sensor interface, the processor having instructions and data stored in the storage medium, the instructions configured such that when executed by the processor cause the system to:
 measure, one or more analyte responsive output signals from a reference sample, wherein the one or more analyte responsive output signals are indicative of an effect of one or more extraneous stimuli on the reference sample, 
 determine a normalizing relationship based on linear or non-linear regression of the one or more analyte responsive output signals; 
 store the normalizing relationship in the storage medium, wherein the normalizing relationship is stored as part of calibration information used for calibrating the biosensor system to account for the one or more extraneous stimuli; 
 responsive to receiving a biological fluid sample, apply an electrical or optical input signal to generate an input signal from the signal generator; 
 generate at least one analyte responsive output signal, wherein the one or more analyte responsive output signals is an electrical output signal generated by a redox reaction or a light-generated output signal in response to a light-identifiable species; 
 determine an initial analyte concentration of the biological fluid sample based on the at least one analyte responsive output signal; 
 determine, using the normalizing relationship, at least one normalized output signal from the at least one analyte responsive output signal; 
 determine a pseudo-reference concentration value of the biological fluid sample, 
 wherein the pseudo-reference concentration value is a substitute for true relative error; 
 determine at least one corresponding normalized output signal by selecting at least one reference sample analyte concentration from a plurality of stored reference sample analyte concentration and a normalized reference correlation; 
 determine a system error for the at least one analyte responsive output signal through a comparison of the initial analyte concentration and the at least one reference sample analyte concentration, 
 wherein the system error contributes to inaccurate analyte concentration determinations; 
 responsive to determining the system error, determine at least one signal-based anchor parameter based on a comparison of the pseudo-reference concentration value and the at least one corresponding normalized output signal, wherein the at least one signal-based anchor parameter compensates for the system error; 
 incorporate the at least one signal-based anchor parameter into a compensation relationship, wherein the compensation relationship compensates for inaccuracies caused by the system error; 
 determine a final compensated analyte concentration of the biological fluid sample based at least in part on the compensation relationship and the initial analyte concentration of the biological fluid sample; and 
 output the final compensated analyte concentration to one or more of a display, a remote receiver, or a storage medium.